Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery

NCT ID: NCT02291419

Last Updated: 2017-02-09

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-31

Study Completion Date

2016-06-30

Brief Summary

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The purpose of this pilot study is to establish the rate of cardiovascular events in patients with elevated troponins levels after major, non-cardiac surgery and to evaluate the efficacy and safety of FDA approved study drug (ticagrelor) compared to aspirin in these patients.

Data from current studies suggest that myocardial injury detected by minor elevations in troponin levels within 3 days after non-cardiac surgery may occur in 10-24% of patients and is associated with an increased risk of mortality at 30 days and 1 year. There are no current guidelines for care of patients with elevated troponin levels in the absence of acute coronary syndrome. This study will assess if the increased risk of these patients is modifiable by an anti-platelet medication and evaluate the safety of this medication.

Patients will be randomized in an open label fashion to receive ticagrelor (anti-platelet medication) or 81 mg. aspirin. Patients will be followed on study treatment for 12 months, with the last contact at one month post treatment discontinuation.

Detailed Description

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The objective of this pilot study is to establish the rate of cardiovascular events in patients with elevated troponins levels post major, non-cardiac surgery and to evaluate the efficacy and safety of ticagrelor treatment compared to aspirin in these patients.

Data from current studies suggest that myocardial injury detected by minor elevations in troponin levels within 3 days after non-cardiac surgery may occur in 10-24% of patients and is associated with an increased risk of mortality at 30 days and 1 year. There are no current guidelines for care of patients with elevated troponin levels in the absence of acute coronary syndrome (ACS) and it is not certain if this is a modifiable disease process. Ticagrelor is a direct, reversible inhibitor of the platelet P2Y12ADP-receptor. It has been shown to be superior to clopidogrel in the setting of ACS. The clinical benefit of treating patients with port-operative troponin elevation with antiplatelet agents remains unexplored. The short half-life of ticagrelor makes it favorable to use in this setting.

This is an open label, randomized, parallel group study comparing ticagrelor to aspirin in patients who experience troponin elevations post major non-cardiac surgery. Patients will be randomized in an open-label fashion to receive either ticagrelor 90 mg twice daily or aspirin 81 mg once daily. Patients will be followed for 13 months post randomization (12 months of treatment and a phone call 30 days after study drug discontinuation). The maximum duration of treatment will be 12 months.

Follow-up visits will occur at Month 1, Month 6, and Month 12. Phone calls will be made at Month 3, Month 9, and at 30 days after study drug discontinuation.

Up to 1000 patients with post-operative troponin elevation ≥2x ULN within first 7 postoperative days, will be enrolled in the study.

Conditions

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Myocardial Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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ticagrelor

ticagrelor 90mg bid

Group Type EXPERIMENTAL

ticagrelor

Intervention Type DRUG

ticagrelor 90 mg bid

aspirin

Patients in the aspirin arm will receive aspirin 81 mg daily orally

Group Type ACTIVE_COMPARATOR

aspirin

Intervention Type DRUG

aspirin 81 mg daily

Interventions

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ticagrelor

ticagrelor 90 mg bid

Intervention Type DRUG

aspirin

aspirin 81 mg daily

Intervention Type DRUG

Other Intervention Names

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Brilinta Bayer, ASA

Eligibility Criteria

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Inclusion Criteria

1. Written informed consent before any study related procedures are performed.
2. A qualifying post-operative T or I troponin elevation (≥2x ULN of assay within 7 days of index surgery and during the index hospitalization).
3. Men and women ≥40 years of age if troponin elevation was identified as part of routine post-operative clinical care OR
4. Men and women ≥55 years of age if troponin elevation was identified post-operatively as part of screening for the study.
5. Undergone non-cardiac surgery requiring an overnight hospital stay.
6. Women of childbearing potential who are sexually active must have a negative pregnancy test at enrollment and agree to use adequate contraception from screening until 30 days after receiving the last dose of study drug.
7. Able to be randomized within 35 days following the index surgery.

Exclusion Criteria

1. Post-operative ST-elevation Myocardial Infarction (STEMI).
2. Post-operative high-risk non-STEMI, defined as patients with elevated troponin with either:

1. active Ischemic EKG changes (≥2 mm of ST-segment depression in at least 2 adjacent leads)
2. ongoing hemodynamic instability thought to be ischemia mediated or
3. persistent anginal symptoms.
3. Planned or urgent coronary angiography/revascularization.
4. A current or ongoing indication for dual antiplatelet therapy (DAPT) as determined by the patient's physician.
5. History of intracranial hemorrhage
6. Bleeding disorder or active bleeding that prevents ticagrelor or aspirin administration.
7. Taking any of the following medications at the time of randomization: vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban , fondaparinux, cilostazol, vorapaxar or LMWHs.
8. Renal dialysis.
9. Hepatic impairment with transaminase ≥3x ULN at time of randomization.
10. Known contra-indication for use of ticagrelor.
11. Estimated life expectancy of \<1 year.
12. Enrolled in another ongoing drug or device research protocol
13. A definite non-ischemic explanation for troponin elevation, such as myocarditis or pulmonary embolism.
14. A documented hypersensitivity to aspirin.
15. Hypersensitivity to ticagrelor or any component of the product.
16. Neurological or ophthalmic surgery during the index hospitalization.
17. Patients taking strong CYP3A inhibitors and/or CYP3A inducers that cannot be stopped for the course of the study.
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

The Cleveland Clinic

OTHER

Sponsor Role lead

Responsible Party

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Venu Menon

MD, FACC, FAHA, Director CICU, CEC-C5, Fellowship Program Cardiovascular Imaging

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Venu Menon, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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University of South Alabama Health System

Mobile, Alabama, United States

Site Status

Arkansas Site Management Service, LLC

Little Rock, Arkansas, United States

Site Status

University of Florida College of Medicine - Jacksonville

Jacksonville, Florida, United States

Site Status

Florida Hospital Orthopaedic Institute and Fracture Care Center

Orlando, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Central Georgia Heart Center

Macon, Georgia, United States

Site Status

Saint Vincent Medical Group

Indianapolis, Indiana, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

McLaren Bay Region

Bay City, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

McLaren Macomb

Mount Clemens, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

New York University School of Medicine

New York, New York, United States

Site Status

Cincinnati VA Medical Center

Cincinnati, Ohio, United States

Site Status

VA Medical Center - Cleveland Louis Stokes

Cleveland, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Oklahoma Heart Institute

Tulsa, Oklahoma, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

VA North Texas Health Care System

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Overlake Hospital Medical Center

Bellevue, Washington, United States

Site Status

Countries

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United States

References

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Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators; Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.

Reference Type BACKGROUND
PMID: 19717846 (View on PubMed)

Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study Investigators; Devereaux PJ, Chan MT, Alonso-Coello P, Walsh M, Berwanger O, Villar JC, Wang CY, Garutti RI, Jacka MJ, Sigamani A, Srinathan S, Biccard BM, Chow CK, Abraham V, Tiboni M, Pettit S, Szczeklik W, Lurati Buse G, Botto F, Guyatt G, Heels-Ansdell D, Sessler DI, Thorlund K, Garg AX, Mrkobrada M, Thomas S, Rodseth RN, Pearse RM, Thabane L, McQueen MJ, VanHelder T, Bhandari M, Bosch J, Kurz A, Polanczyk C, Malaga G, Nagele P, Le Manach Y, Leuwer M, Yusuf S. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012 Jun 6;307(21):2295-304. doi: 10.1001/jama.2012.5502.

Reference Type BACKGROUND
PMID: 22706835 (View on PubMed)

POISE Study Group; Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC, Xavier D, Chrolavicius S, Greenspan L, Pogue J, Pais P, Liu L, Xu S, Malaga G, Avezum A, Chan M, Montori VM, Jacka M, Choi P. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008 May 31;371(9627):1839-47. doi: 10.1016/S0140-6736(08)60601-7. Epub 2008 May 12.

Reference Type BACKGROUND
PMID: 18479744 (View on PubMed)

Horr S, Reed G, Menon V. Troponin elevation after noncardiac surgery: Significance and management. Cleve Clin J Med. 2015 Sep;82(9):595-602. doi: 10.3949/ccjm.82a.15076.

Reference Type DERIVED
PMID: 26366956 (View on PubMed)

Other Identifiers

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CCAZ-2014

Identifier Type: -

Identifier Source: org_study_id

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